The cardioprotective effect of urocortin during ischaemia/reperfusion involves the prevention of mitochondrial damage

Kevin M Lawrence; Paul A Townsend; Sean M Davidson; Christopher J Carroll; Simon Eaton; Mike Hubank; Richard A Knight; Anastasis Stephanou; David S Latchman

doi:10.1016/j.bbrc.2004.06.170

The cardioprotective effect of urocortin during ischaemia/reperfusion involves the prevention of mitochondrial damage

Biochem Biophys Res Commun. 2004 Aug 20;321(2):479-86. doi: 10.1016/j.bbrc.2004.06.170.

Authors

Kevin M Lawrence¹, Paul A Townsend, Sean M Davidson, Christopher J Carroll, Simon Eaton, Mike Hubank, Richard A Knight, Anastasis Stephanou, David S Latchman

Affiliation

¹ Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. [email protected]

PMID: 15358201
DOI: 10.1016/j.bbrc.2004.06.170

Abstract

We have previously shown, using Affymetrix gene chip technology, that urocortin induces the expression of several diverse genes in cardiac myocytes. An ATP sensitive inwardly rectifying potassium channel, Katp (Kir6.1), the enzyme calcium independent phospholipase A2 (iPLA2), and protein kinase C epsilon (PKCepsilon) and that these genes are involved in the cardioprotective mechanism of action of urocortin. Here we demonstrate that these gene products are localized to cardiac myocyte mitochondria and for the first time show that urocortin protects cardiac myocytes from ischaemia/reperfusion induced cell death by preventing mitochondrial damage. Using pharmacological agents to Katp channels and iPLA2 and synthetic peptide inhibitors of PKCepsilon, we go on to demonstrate that these three gene products are involved in the urocortin induced protection of cardiac myocyte mitochondria. These proteins may interact at the mitochondria to produce the protective effect.

MeSH terms

Aldehydes
Animals
Cardiotonic Agents / pharmacology*
Cells, Cultured
Corticotropin-Releasing Hormone / pharmacology*
Intracellular Membranes / drug effects
Intracellular Membranes / metabolism
Microscopy, Fluorescence
Mitochondria, Heart / drug effects*
Mitochondria, Heart / enzymology
Mitochondria, Heart / metabolism
Mitochondria, Heart / pathology*
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / metabolism
Myocytes, Cardiac / pathology
Phospholipases A / metabolism
Phospholipases A2
Potassium Channels, Inwardly Rectifying / metabolism
Protein Kinase C / metabolism
Protein Kinase C-epsilon
Rats
Rats, Sprague-Dawley
Reperfusion Injury / enzymology
Reperfusion Injury / pathology*
Reperfusion Injury / prevention & control*
Rhodamines
Urocortins

Substances

Aldehydes
Cardiotonic Agents
Potassium Channels, Inwardly Rectifying
Rhodamines
Urocortins
mitotracker green FM
tetramethylrhodamine methyl ester
Corticotropin-Releasing Hormone
Prkce protein, rat
Protein Kinase C
Protein Kinase C-epsilon
Phospholipases A
Phospholipases A2